Mechanical extension implants for short bowel syndrome

ABSTRACT

A bowel extension device implantable into a body for treatment of short bowel syndrome. The bowel extension device comprises a housing and a displaceable member coupled to the housing. The bowel extension device is configured to apply a tensile force sufficient to promote bowel growth without causing damage to the bowel. In some embodiments, the bowel extension device can be completely contained with the body.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation-in-part of U.S. patent applicationSer. No. 11/673,193 filed on Feb. 9, 2007. This application also claimsthe benefit of U.S. Provisional Application No. 61/043,549 filed on Apr.9, 2008. The entire disclosures of each of the above applications areincorporated herein by reference.

FIELD

The present disclosure relates to mechanical extension implants and,more particularly, mechanical extension implants for use in the linearextension of the gastrointestinal tract; including the esophagus, smallintestine, and large intestine.

BACKGROUND AND SUMMARY

The statements in this section merely provide background informationrelated to the present disclosure and may not constitute prior art.

Short-bowel syndrome (SBS) is a devastating disease associated withmortality rates exceeding 30%. It is a condition where the smallintestinal length is far less than required for proper nutrientabsorption. This condition can occur in pediatric and adult populations,and may be due to congenital processes, or acquired through the loss oflarge amounts of small intestine due to inflammatory conditions orischemic events. The syndrome prevents a self-sustaining absorption ofnutrients from the intestine, and supplemental parenteral nutrition isrequired. An estimated 40,000 patients with intestinal dysfunction fromsmall bowel syndrome require parenteral nutrition. Several long-termeffects due to parenteral nutrition have been found to be harmful, suchas sepsis, liver disease, and bowel bacterial overgrowth; therefore,this method can only be used as a short-term solution. Care for smallbowel syndrome patients is in excess of $200,000 per patient per year,and estimated costs in the United States have exceeded $1 billionyearly.

A number of treatment procedures have been proposed to alleviate smallbowel syndrome. Some have tried using growth hormones along withspecific nutrients known to stimulate bowel tissue growth. This approachhas limited effectiveness and several obstacles, including reversal ofthe adaptive process after termination of the hormones, lack of somaticmuscle growth, and concerns about uncontrolled and tumorous growth.

Another option is to surgically modify the organs to achieve an increasein intestinal length. With this approach, there is a risk of injury tothe mesenteric vasculature, leakage of enteric contents due to a verylong surgical connection, and the procedures can only be done if theintestine is overly dilated. Despite success in some patients, there isa very high failure rate up to 45% in some series.

Finally, small bowel transplantation has been used for adults andchildren when other treatments have failed. Although a viable option,transplantation is very costly. Patients require long-termimmunosuppression and are at risk for infection and graft failure.Although early patient and graft survival are excellent, five-year graftsurvival is typically at the 50% level, and patient survival isapproximately 60%. Clearly, there is a great need for an alternativeprocedure to treat short bowel syndrome.

Recently, the principles of the present teachings have demonstrated thatmechanical forces can be powerful regulators of tissue growth orregeneration. Through the process of mechanotransduction—the translationof mechanical signals to biochemical ones which affect cell function—theresponse to the forces results in a cascade of actions which includesthe activation of growth mechanisms. Numerous organs have been shown tobe mechanoresponsive including bone, lung, and neural tissue. Accordingto the principles of the present teachings, the controlled mechanicalstimulation to the small intestine, such as through mechanotransductionof forces applied in a linear fashion to small bowel, can help induceintestinal growth.

According to the principles of the present teachings, implantable bowelextenders are provided that can be used to overcome the issuesassociated with small bowel syndrome. In some embodiments, theimplantable bowel extender can be a hydraulic and/or a shape memoryalloy (SMA) actuated device.

Further areas of applicability will become apparent from the descriptionprovided herein. It should be understood that the description andspecific examples are intended for purposes of illustration only and arenot intended to limit the scope of the present disclosure.

DRAWINGS

The drawings described herein are for illustration purposes only and arenot intended to limit the scope of the present disclosure in any way.

FIG. 1 is a graph illustrating force displacement characteristics ofvarious portions of a small bowel where the dashed sloped indicates asafe range of force/displacement to avoid damage to the bowel;

FIG. 2A is a schematic view illustrating a hydraulic bowel extenderaccording to the present teachings in a retracted position;

FIG. 2B is a schematic view illustrating the hydraulic bowel extender ofFIG. 2A in an extended position;

FIG. 3 is a photograph of a hydraulic bowel extender according to theprinciples of the present teachings;

FIG. 4 is a perspective view illustrating a bowel extender according tothe present teachings using a shape memory allow (SMA) drive system;

FIGS. 5A-5E is a series of partial cross-sectional views illustratingthe SMA bowel extender of FIG. 4 through a drive cycle;

FIG. 6 is a cross-sectional view illustrating a bowel extender accordingto the present teachings using an SMA drive system to extend in opposingdirections;

FIG. 7 is a perspective view illustrating a bowel extender according tothe present teachings being implantable within a bowel without the needto remove a segment of the bowel from the digestive tract;

FIGS. 8A-8C is a series of cross-sectional views illustrating placementof the bowel extender of FIG. 7 within a body and the progressive stepsof such bowel lengthening process;

FIG. 9 is a schematic view illustrating various extension configurationswhen disposed in a body cavity;

FIG. 10 is a side view, with portion hidden, of an outer syringe casingaccording to the present teachings;

FIG. 11 is a rear view of the outer syringe casing according to thepresent teachings;

FIG. 12 is a front view of the outer syringe casing according to thepresent teachings;

FIG. 13 is a side view, with portion hidden, of an inner syringe casingaccording to the present teachings;

FIG. 14 is a rear view of the inner syringe casing according to thepresent teachings;

FIG. 15 is a front view of the inner syringe casing according to thepresent teachings;

FIG. 16 illustrates a handcuff embodiment of a clamping attachment,where the handcuff mounts around the outside of the bowel clamping itagainst the groove of the implanted device;

FIG. 17 illustrates a suction puck embodiment of a suction attachment,where suction is produced at the holes (by, for example, an SMA actuatedbellows) around the disk's circumference, holding the bowel from theinside;

FIG. 18 illustrates a fish scale embodiment of a friction attachment,where directionally selective friction is produced by a series ofscale-like surface features can push the bowel in one direction,producing tension, but allow free motion in the other;

FIG. 19 illustrates a conveyor belt concept, where continuous paying outof the bowel is produced by traction developed by moving conveyor beltsacting through friction on the bowel wall;

FIG. 20 illustrates an SMA ratchet driven conveyor, where the conveyorfor continuous paying out can be actuated by a reciprocating SMA—springpair acting through a ratchet mechanism on the belt;

FIG. 21 illustrates a track-follower device in body cavity, which is aCAD rendering of track-following bowel extender inside abdominal cavitytaken from CT-scan data;

FIG. 22 illustrates an SMA ratchet track crawler, where an SMA-drivenratchet causes a crawler to incrementally moving along a trackstretching the bowel over the length of the track;

FIG. 23 illustrates details of crawler, where ratchet flaps allow motiononly forward along the track enabling ratcheting driven by the SMAwire/spring pair;

FIG. 24 illustrates the ratcheting operation of the crawler, wherereciprocating motion of the SMA-spring pair produces incremental forward(leftward) motion of the crawler along the track;

FIG. 25 illustrates the SMA ratchet track crawler housing, where thetrack crawler is implanted in continuity with the bowel, and thereforemust have channels and holes through which fluids may flow;

FIG. 26 illustrates the SMA ratchet track crawler housing, where thetrack crawler is implanted in continuity with the bowel, and thereforemust have channels and holes through which fluids may flow;

FIG. 27 illustrates the cable-driven passive expander, where anSMA-driven pulley unwinds a cable winch which allows a spring to expandand apply tensile forces to the bowel;

FIG. 28 illustrates the rotating-disc spring expander, where a spring isallowed to expand as a disc through which it is threaded rotates asallowed by an SMA driven spring-escapement mechanism;

FIG. 29 illustrates the SMA escapement of the rotating-disc springexpander, where reciprocating motion of an SMA wire (red/blue)-spring(orange) pair moves a sliding element (blue) to incrementally engagealternately opposing teeth on a barrel-shaped escapement (yellow) whichallows the coil spring (magenta) to incrementally unwind; and

FIG. 30 illustrates a distributed SMA scissor mechanism, where a seriesof scissor mechanisms are individually actuated to cause incrementalexpansion of the whole device.

DETAILED DESCRIPTION

The following description is merely exemplary in nature and is notintended to limit the present disclosure, application, or uses.

Bowel extenders according to the principles of the present teachings,generally indicated at 10 in the accompanying figures, are designed tooperate inside the human body cavity inserted in a section of bowel,which can remain intact in the digestive tract, or can be detached fromthe digestive tract yet remain attached to the vasculature. In caseswhere a section of bowel is detached, the remaining bowel can bereattached, thereby maintaining bowel function during the lengtheningprocess. Bowel extender 10 extends gradually, and after treatment, thelengthened bowel segment can be anastomosed back into the digestivetract. It should be appreciated that the power, monitoring, andautomatic control components can be integrated within the implanteddevice.

For clinical use, the implant design should meet a set of specificationsbased on the mechanical and growth properties of the bowel itself andthe body cavity. To fit inside an average-sized adult human bowel, bowelextender 10 may have an outside diameter ranging from 1 cm to 2 cm,allowing enteric fluids and mucous to transit around the device. Bowelextender 10 should be relatively smooth, made of biocompatiblematerials, and should not generate external temperatures greater than37° C. to avoid damaging the bowel tissue. The un-extended length of abowel extender 10 which is placed in an isolated segment of bowel shouldrange from 10 cm to 15 cm. For extenders which are placed into thenormal continuity of the intestine, longer segments may be lengtheneddepending on the abdominal cavity dimensions of each patient. However,it should be appreciated that various sizes of bowel extender 10 may bemanufactured for various sizes of patients. Ideally, the implant shouldextend to a minimum of twice its initial length, although furtherextension is always desirable and less extension may be acceptable insome cases.

To determine the forces required to stretch the bowel and the maximumforce to avoid bowel damage, mechanical tests were conducted on sectionsof pig bowel similar in dimension to human bowel. A series of tensileloads were applied to a set of 10 cm bowel segments taken from variouslocations along the intestinal tract, and the relative change in length(strain) was measured. As illustrated in FIG. 1, the force-strainrelationships plotted show a linear elastic region at loads below 10 gf(gram-force) above which the bowel becomes less stiff. Inspection of thebowel shows that no damage occurs at tensile loads below 35 gf andstrains below 20%.

A key function of bowel extender 10 is to maintain the tensile force asthe bowel grows, thus a static device is not sufficient because as thebowel grows it could lose contact with the device. Additionally, due tothe slow growth rate of the bowel, the extension rate of bowel extender10 does not need to be rapid and, thus, can be on the order of about 1cm per day. This motion may be continuous, such as in connection with ahydraulic extender, or can define finite steps, such as in connectionwith an SMA actuated extender (each will be discussed in detail below).

For the finite step scenario, bowel extender 10 should hold the newlength for a period of time after each step, such that the bowel cangrow and “catch up” with bowel extender 10 before another step is taken.In some embodiments, these steps can occur when the patient is or knownto be still. At other times, however, the patient may be moving, suchthat when holding a position, bowel extender 10 must hold against forcesfrom the surrounding tissues larger than those occurring during a step,with a specified retention force set to 200 gf.

While the 35 gf safe limit allows a large, 2 cm step size, in practice,a smoother and slower lengthening is desired, with a 1 to 2 mm step sizespecification. A 2 mm step represents a 2% strain on a 10 cm bowelsegment, with a corresponding tensile force of 1.4 gf. This, however, issimply the force required to stretch the bowel; additional force isrequired to push against the soft tissues surrounding the bowel.Therefore, the required extension force can be set to a range of 15 to35 gf.

In some embodiments, bowel extender 10 can be used for extension onlyand thus need not be capable of retraction. However, it is anticipatedthat bowel extender 10 can be constructed to have a retraction functionto aid in its removal.

Hydraulic Bowel Extender

In some embodiments of the present teachings, a clinically appropriateimplantable bowel extension device is provided and generally referencedas a hydraulically-actuated bowel extender 10. Bowel extender 10 wasused in connection with in-vivo lengthening experiments in pig smallbowel as illustrated in FIGS. 2 and 3.

3.1. Device Architecture

Hydraulics provide a simple means of direct linear extension. Inprinciple, a hydraulic piston can produce large motions with largeforces as long as a high-pressure fluid source is available which can bedifficult to implant, requiring connection through the skin to anexternal fluid source. The overall motion of a hydraulic piston islimited by the length of the cylinder, and is reduced by the additionallength required for piston seals and hydraulic connection ports. Toovercome the effects of this extra overhead and come near to the goal ofa length-doubling extension, a dual concentric piston design wasdeveloped which provides approximately twice the motion of a singlepiston in a similar package size.

Bowel extender 10 (shown schematically in FIG. 2 and in the photographin FIG. 3) comprises an outer syringe casing 12 (cut from a 3 ml, 10.2mm diameter medical syringe) through which an outer syringe plunger 14runs. The outer syringe plunger 14 is attached to and pushes forward aninner syringe 16 (cut from a 1 ml, 6.4 mm diameter medical syringe)through which another rubber plunger 18 runs. The inner syringe rubberplunger 18 pushes forward a push rod 20 which extends to the forward endof bowel extender 10. Silicone bumpers 22, which can be about 16 mm indiameter, on the back end 24 of outer syringe 12 and the front end 27 ofpush rod 20 apply extension forces against the ends of the bowelsection. When saline fluid (chosen for biocompatibility) is forced intobowel extender 10 using a manually operated unmodified 10 ml syringe oractuation piston 30 as a pump, pressure from fluid in outer syringe 12pushes forward the outer syringe plunger 14. A hole 15 through the outersyringe plunger 14 allows fluid to flow into inner syringe 16, pushingthe inner syringe plunger 18 and push rod 20 forward. In someembodiments, the overall length of bowel extender 10, when retracted, is11.8 cm. Outer piston system 26, including outer syringe 12, outersyringe plunger 14, and inner syringe 16, extends 5.7 cm beyond thislength, and inner piston system 28, including inner syringe 16, plunger18, and push rod 20, extends an additional 4.5 cm, for a total extendedlength of 22.0 cm: an 86% increase in length. It should be appreciatedthat bowel extender 10 can be configured with additional piston systemsto achieve greater extension, such as 4-, 5-, or more fold.

3.2. Benchtop Characterization

Benchtop tests were performed to validate the basic operation of thedual hydraulic embodiment of bowel extender 10 and to determine both theforces on actuation piston 30 required to produce motion and the holdingpower of bowel extender 10. Because of the large diameter of actuationpiston 30, relatively large forces are required to actuate bowelextender 10 to overcome friction in the pistons and to produce motion.To measure these forces, actuation piston 30 was mounted vertically in avice and increasingly large weights placed on the actuation piston 30until motion was produced in bowel extender 10. Since the diameter ofouter piston system 26 was larger than the diameter of the inner pistonsystem 28, the outer piston system 26 moved first, requiring a 2200 gfweight on actuation piston 30. Once actuation piston 30 reached its fullextension, weight was gradually added until a total of 6900 gf of weightcaused inner piston system 28 to move to its full extension. The 2200 gfweight corresponds to a fluid pressure of 103 kPa gage (15 psi), or aforce of 640 gf on outer piston system 26 to overcome friction.Similarly, the 6900 gf of weight corresponds to a fluid pressure of 324kPa gage (47 psi), or a force of 648 gf on inner piston system 28 toovercome friction. To measure the holding capacity of bowel extender 10,when actuation piston 30 is left free to move, bowel extender 10 waspushed against a digital scale until each piston retracted. Inner pistonsystem 28 retracted first, with a force of 400 gf, twice the required200 gf, after which outer piston system 26 retracted with a force of 900gf.

3.3. In-Vivo Experiments

A population of eleven (11) young adult pigs was implanted with the dualhydraulic embodiment of bowel extender 10. In each pig, two 11 cmlengths of bowel were isolated from the digestive tract (suspended onits mesentery), and the remaining bowel reconnected. Both segments had ahydraulic extender inserted, and the ends were oversewn. The tubingwhich connected to actuation piston 30 was brought out through one end.One of the two segments acted as a control, and no fluid was pumped intobowel extender 10. The other underwent an incremental lengthening (0.5ml, or approximately 1.46 cm per day) over the course of seven days,until bowel extender 10 was fully extended (10.2 cm). All but one pighad a successful trial: the first pig developed an intestinal leak dueto a buildup of mucus, which was drained in the remaining 10 pigs, andthis initial pig had to be sacrificed on the third day of extension.

After the extension procedure, the small bowel segment length, weight,and surface area were compared between the control segments and theextended segments in Table 1:

Length Wet Weight Surface area Group (cm) (g) (cm²) Mass/cm² Control10.4 ± 3.2  17.4 ± 4.5  46.1 ± 13.7  0.33 ± 0.04 Lengthened 17.6 ± 2.4*29.4 ± 2.3* 86.7 ± 19.8* 0.28 ± 0.03As can be seen from the table above, the lengthened segments were 69%longer, 69% heavier, and include 88% more surface area relative to theControl segments. Additionally, the mass per cm² decreased onlyslightly, by 15%, indicating that the lengthened bowel has potentiallysimilar structure and function to normal intestine.

3.4 Preliminary Data On Implanted Devices

Histology: Mucosal thickness and crypt depth was much greater in theLengthened group versus the Control group as illustrated in Table 2:

TABLE 2 Villus height Crypt depth Mucosal thickness Group (μm) (μm) (μm)Control 324 ± 76 365 ± 43 647 ± 75 Lengthened 353 ± 76  450 ± 95*  772 ±134 Jejunum 522 ± 87 341 ± 64 842 ± 75Villus heights, however, were reduced in both the Lengthened and Controlgroups compared to the adjacent jejunal segment; most likely becauseboth segments were taken out of continuity with normal enteric flow. Incontrast, crypt depth dramatically increased in the Lengthened segmentcompared to both the Control and jejunal segments. Increased crypt depthwas accompanied by an increase in epithelial proliferation. Epithelialcell (EC) proliferation (% of proliferating crypts) showed a significant(P<0.05) increase in crypt cell proliferation in the Lengthened(26.30±3.3) versus the Control (15.67±5.70) and adjacent jejunal(12.09±5.9) groups. Importantly, gross and histologic inspection did notshow evidence of mechanical injury to the lengthened segments of bowel.

Physiologic changes after lengthening: DNA and RNA content did notdiffer between the Lengthened and Control groups. Ussing chamber studieswere performed to assess the mucosal epithelial absorption andepithelial secretory function, as well as epithelial barrier function ofthe Lengthened segment. The Lengthened group, in this case was comparedto normal jejunum, in order to determine the differences and/orsimilarities between normal functioning bowel and the elongated segment.Epithelial barrier function in Lengthened versus normal jejunum weremeasured by changes in transepithelial passage of [3H]-mannitol andtransepithelial resistance (TER). Transepithelial passage of[3H]-mannitol remained unchanged. However, a decline in barrier functionwas observed when measured by transepithelial resistance (TER) asillustrated in Table 3:

TABLE 3 Glucose-mediated Carbachol- [3H]- sodium transport mediatedchloride Group mannitol TER (μA/cm²) transport (μA/cm²) Jejunm 0.16 ±0.08 11.5 ± 0.9  18.1 ± 5.4   11.4 ± 2.9 Lengthened 0.17 ± 0.08 10.2 ±0.4* 8.8 ± 2.0** 11.8 ± 2.9Carbachol-induced epithelial chloride transport was not significantlydifferent compared to normal jejunum (P=0.67). Glucose-mediatedepithelial sodium transport, however, was decreased in the Lengthenedgroup compared to normal jejunum.

Investigation into the mechanisms responsible for enterogenesis: Basedon previous work with mechanotransduction models in various organsystems, a number of factors were identified that, at least in part,might be responsible for mediating the growth of the small bowel inthese experiments. The mRNA expression of several factors derived frommucosal scrapings of Lengthened and Control segments of bowel isillustrated in Table 4:

TABLE 4 Alpha-E E- Hedgehog Group Occluden Proglucagon integrin C-SrcWnt5a Cadherin (Indian) Control 0.89 ± 0.09 0.42 ± 0.18 0.58 ± 0.07 0.28± 0.01 0.08 ± 0.02 0.27 ± 0.02 0.28 ± 0.07 Lengthened 0.98 ± 0.09 0.55 ±0.22 0.58 ± 0.20  0.43 ± 0.10*  0.16 ± 0.04* 0.32 ± 0.04 0.29 ± 0.14Of note was a significant (2-fold) increase in the expression of C-Srcand Wnt in the Lengthened group. Wnt 5 a was selected as a known inducerof intestinal embryogenesis 1, 2. E-Cadherin and proglucagon (precursorto GLP-2) increased, but changes were not significant. This suggeststhat both Integrin-mediated and Wnt signaling pathways which may helpmediate distraction-induced enterogenesis in this pig model.

Protein Expression: Differential protein analysis of factors expressedin the Lengthened versus Control group was performed with 2-D gelelectrophoresis (University Protein Core, N=3). A secondary massspectrogram analysis was performed (Applied Biosystems, Foster City,Calif.) of 6 proteins which were only expressed in the Lengthened group.This included an expansion of desmin, vimentin and beta actin profilincomplex. Other proteins which may or may not have relevance toenterogenesis include: alpha-1-antichymotrypsin, condensin subunit 1 andimmunoglobulin lambda-chain. The finding of increased desmin andvimentin (expression>95% confidence interval) strongly supports aWnt-mediated signaling pathway as these factors are exclusivelyexpressed in the mucosa of developing intestine during increased Wntexpression.

While further study is required to determine the function of thelengthened bowel relative to normal intestine, the hydraulic extender 10clearly demonstrates that an implantable extension device has thepotential to become a useful clinical device for treatment of shortbowel syndrome, and is worthy of further development and testing.However, the foregoing should not be interpreted as precluding the useof the hydraulic bowel extender 10, but rather simply enumerating thatadditional modification can be made to the present teachings withoutdeparting from the spirit of such teachings.

3.5. Reimplantation of Lengthened Bowel into the Normal Continuity ofthe Intestine

Rationale: It has been shown herein that according to the principles ofthe present teachings, the length of an isolated intestinal segment canbe doubled with the application of linearly directed distractive forcesover a predetermined time period (such as 7 days), thus resulting inincreased surface area and epithelial cell proliferation. In order toevaluate the function of these lengthened segments after re-implantationinto normal jejunum, reimplantation of the lengthened segment wasperformed.

Methods: Bowel extender 10 was inserted into isolated jejunal segmentsin pigs, and fully expanded over 8 days. A control intestinal segmentcontained bowel extender 10, but was not lengthened. Lengthenedsegments, numbering five (5) in total, were then re-implanted intonormal intestinal continuity. Pigs were sacrificed after another 28days. Function was assessed by motility and absorptive capacity of thebowel. Data (mean±SD) were analyzed using ANOVA and t-test;*P<0.05.

Results: Lengthened segments were significantly longer than controlsegments and had a nearly 2-fold greater surface area. Bowel lengtheningwas maintained, going from 9.4±1.7 cm at re-implantation to 11.3±1.9 cmafter 28 days. Motility was assessed by upper GI transient time andpassage of activated charcoal. Motility was similar to non-operated pigs(Upper GI, 5.4±0.8 hours versus 6.3±0.6 hours; re-implanted versusnon-operative, passage of activated charcoal, 17.6±1.7 hours versus17.1±1.3 hours). Smooth muscle cells (2.5×104) were harvested fromlengthened bowel and assessed for contractility 30 seconds afterapplication of acetylcholine. A transient decline in function was seenafter 8 days of lengthening (24.5±0.5 versus 51.6±1.0; % contractionfrom baseline in lengthened versus non-operated bowel); howevercontractility began to approach normal levels (38.3±0.9 versus 50.2±1.0)after re-implantation. Table 5 shows disaccharidase expression in themucosa, and shows that these levels (which represent the absorptivecapacity of the gastrointestinal tract) return to normal levels once thelengthened segment is replaced back into the normal continuity of thegastrointestinal tract.

TABLE 5 Lactase Sucrase Isomaltase Maltase Normal 34.7 ± 13.7 36.3 ±11.6 33.1 ± 13.0 120.2 ± 49.5 Lengthened 13.6 ± 4.8* 21.8 ± 6.8  25.4 ±13.2 106.6 ± 38.2 Re-implanted 30.8 ± 6.2  41.3 ± 18.5 42.1 ± 12.2114.04 ± 4.5 

Chamber experiments were done to further assess the absorptive capacity(Table 6). Similarly, although there are some losses of ion transportfunction immediately after the bowel is lengthened, these return tosimilar values to normal bowel once the lengthened segment is returnedto the normal gastrointestinal continuity.

TABLE 6 Baseline current Ion-transport (μA/cm2) BF(%) (μA/cm2) Na+ Cl−Normal 0.13 ± 0.04 11.0 ± 1.6  19.0 ± 4.0 16.9 ± 2.9 Lengthened 0.13 ±0.04  8.9 ± 2.2#  12.2 ± 2.2#  11.4 ± 3.0# Re-implanted 0.13 ± 0.04 9.8± 3.8 18.4 ± 3.7 12.5 ± 3.7

Accordingly, it should be appreciated from the foregoing that bowellengthening, according to the present teachings, results in a transientdecline in mucosal absorptive function and smooth muscle contractility,while maintaining barrier function. However, function approaches that ofnormal bowel after re-implantation into enteric flow. Further, the gainin length is preserved after re-implantation.

4. Shape Memory Alloy (SMA) Bowel Extender

Due to the compactness and implantability requirements of bowelextenders in many cases, conventional approaches are not viable dueeither to a) the external equipment necessary to drive them as in thecase of hydraulics, or b) to their large size, such as in the case ofelectromechanical actuators. However, it should be appreciated that sucharrangements are not to be regarded as being outside the scope of thepresent teachings and are intended to be part of the present disclosure.Shape memory alloy is an attractive alternative because it is unmatchedon specific power (>100 kW/kg) and specific work (up to GJ/m3), andsimultaneously produces high strains (3-8%) and high stresses (up to 50GPa), which is necessary for very compact actuation systems as requiredin the bowel extender. SMA also operates at safe levels of voltage andcurrent to activate via resistive heating, is relatively inexpensive,and extremely biocompatible and corrosion resistant. The maindisadvantage of SMA is its inherent slowness, typically only a fewhertz, resulting from the heating and cooling activation cycle.Fortunately, in this case, the desired response is slower than this andthe heat can be mitigated via a thin layer of thermal insulation or byembedding the SMA material within the interior of bowel extender 10. Thechallenge in the design of SMA wire 112 based bowel extender is totransform the relatively small strains (3-8%) into a long, continuousmotion (over many cm). To achieve this, a ratcheting approach based uponmany cyclic steps was pursued.

4.1. Device Architecture

In general, shape memory alloys (SMA) undergo first-order diffusionlessdisplacive transformations. When SMA's are heated they revert to theiroriginal Austenite form, regaining any strain imposed at lowertemperatures when it is in its soft Martensite phase. An actuator(motor) can be formed by coupling the SMA with a spring that inducesstrain in the wire as it cools to its Martensite phase. Because theactuation strain in the SMA is limited to only a few percent, a linearratcheting extension mechanism was conceived to accumulate theseincremental motions to produce large displacements.

The basic design of SMA wire 112 bowel extender is a concentric tubularlinear ratcheting mechanism, as illustrated in FIGS. 4-7, where a steelthreaded push rod 100 slides inside a stainless steel outer shell 102,which has a ratchet flap 104 which engages in push rod 100 threads 106.A stainless steel movable collar 108 slides on outer shell 102 and alsohas a ratchet flap 110 which engages in push rod 100 threads 106.Ratchet flap 104 and ratchet flap 110 are designed such that they allowmotion of push rod 100 in the extension direction only. An SMA (Nitinol)wire 112 is used as the actuator which, upon heating to the Austenitephase, can contract by 3-8% of its initial length. SMA wire 112 worksagainst a return spring 114 which, when SMA wire 112 cools, stretchesSMA wire 112 back to its initial length.

The resulting cyclic linear motion is used to actuate the ratchet systemof ratchet flap 104 and ratchet flap 110, as shown in FIGS. 4-7. Duringthe forward motion, the Austenitic SMA wire 112 (a) pulls the movablecollar 108 forward (b) relative to outer shell 102, and pushes push rod100 along with it due to collar ratchet flap 104 engagement (c), whilethe shell ratchet flap 110 disengages (d), allowing push rod 100 toslide forward (e). This motion compresses return spring 114 (f). Whenfully actuated, both movable collar 108 and push rod 100 have movedforward a distance Δ, return spring 114 is fully compressed (g), and theshell ratchet flap 110 reengages (h). As SMA wire 112 cools (i), returnspring 114 stretches it back out, pushing the movable collar 108 backrelative to outer shell 102 (j). During this motion, the shell ratchetflap 110 (k) holds push rod 100 in place (l) while collar ratchet flap104 disengages (m), allowing movable collar 108 to slide back to itsoriginal position, after which movable collar 108 flap reengages (n) andreturn spring 114 is extended back to its original length. The neteffect of this motion is to incrementally move push rod 100 forward byone or more thread teeth relative to outer shell 102. The front end ofpush rod 100 and the rear end of outer shell 102 thus push against theends of the bowel segment, extending it.

4.2. Device Design

In the design of bowel extender 10, it is helpful to balance SMA wire112 and return spring 114. During actuation, SMA wire 112 must be strongenough to compress return spring 114, overcome friction in themechanism, and apply the specified 20 gf bowel load. During reset,return spring 114 must be designed to be just strong enough to stretchSMA wire 112 and overcome friction in the mechanism. While the frictionforce varies as the tooth engages and disengages with the ratchet, amaximum 379 gf load was measured and can be used as a conservative valuefor design purposes. An 8 mil diameter SMA wire 112 was chosen since itwas experimentally determined to be capable of producing over 1600 gf offorce. The 90 mm length of this wire was selected to be as long as canbe reasonably mounted in bowel extender 10.

SMA wire 112 material lines were measured by gradually applying atensile load and measuring deflection of both a cool (Martensitic) wireand an electrically heated (Austenitic) wire. A stock 53.6 gf/mmcompression spring was selected with 9.14 mm diameter and 28.6 mmuncompressed length capable of producing forces up to 800 gf. Thepreload on return spring 114 was selected to stretch the wire to amaximum of 4% strain (requiring 137 gf), for a total force of 546 gfincluding friction and bowel load. After a 15% safety factor in resetwas added, a 17 mm compressed length was used.

4.3. Prototype

A prototype was developed to test the principles of the presentteachings. To this end, movable collar 108 and outer shell 102 wereconstructed from 0.25 mm wall thickness stainless steel tubing withflaps and tabs cut in. Push rod 100 was cut from standard 6.35 mm (0.25in) diameter 1.27 mm (0.05 in) thread pitch (and equivalently singlestep size) stainless steel threaded rod. SMA wire 112 was attached atthe leading edge of outer shell 102 and at the trailing end of movablecollar 108. At the leading edge of movable collar 108, a flap was bentup to which SMA wire 112 was soldered using Nitinol Flux 400™ from ShapeMemory Applications Inc., electrically connecting it to the bulk ofbowel extender 10. Since the two ends of SMA wire 112 must beelectrically isolated, the trailing end of movable collar 108 SMA wire112 slips through a small slot in an additional Teflon collar andattaches to a rectangular brass crimp at the end of the slot, providinginterference. This Teflon collar is the largest diameter feature onbowel extender 10 with an outer diameter of 10 mm. Electrical connectionwires were soldered to the solder joint at the leading edge and to thebrass crimp at the trailing end. Lumps of epoxy were attached to thefront end of push rod 100 and the back end of outer shell 102 to providesmooth pushing surfaces.

The retracted length of bowel extender 10, and consequently both pushrod 100 and outer shell 102, is about 10 cm. However, it should beappreciated that other lengths and sizes can be used depending upon thesize of the patient or animal. While ideally, the full extended lengthof bowel extender 10 would be equal to the length of push rod 100 plusthe length of outer shell 102 (a total of 20 cm), push rod 100 mustremain engaged with both ratchet flap 104 and ratchet flap 110, notingthat movable collar 108 flap lies behind return spring 114. Also, tomaintain structural rigidity, push rod 100 must be partially retractedinto outer shell 102. Thus, a certain degree of overhead is required anda full doubling in length is not possible. In this case, an 18 mmoverhead length was required, allowing bowel extender 10 to extend to atmaximum length of 18.2 cm, or 82% longer than its initial length.

4.4. Experimental Setup

To validate the design and performance of bowel extender 10, theprototype was tested to evaluate its ability to produce step motionunder load. A test stand was used that allows the application ofspecified compressive loads to the end of bowel extender 10 duringactuation and subsequent measurement during motion. The prototype devicerests horizontally on a nylon bearing cylinder with the trailing endbutted against an aluminum bracket. A variable weight hanging over theedge of the bench applies a compressive load to bowel extender 10 via awire routed over a pulley and looped over the leading end of push rod100. A non-contact MICROTRAK 7000 laser displacement sensor measures thedeflection of the end of push rod 100. The data from the displacementtransducer is recorded by a PC running Labview by means of an MIO-16EI/O board. Current is applied to SMA wire 112 from a KEPCO programmableDC power supply. The power supply was programmed to apply a square pulsein current of specified amplitude and time, and both the power input andbowel extender 10 motion were measured. The 0.8 A current used wasdetermined empirically as the smallest current over which no additionmotion occurs, fully transitioning the wire. Sequential steps wereapplied by cycling the current on for 10 seconds and then off for 20seconds, giving plenty of time for SMA wire 112 to both heat and cool.Two sets of experiments were run to validate the operation andperformance of bowel extender 10. First, external loads similar to thoseseen in stretching the bowel (0 to 50 gf) were applied and the steppingperformance evaluated. Second, the ability of bowel extender 10 to stepunder larger loads (0 to 400 gf) was evaluated to determine the overallcharacteristics of bowel extender 10.

4.5. Benchtop Results

When actuated, bowel extender 10 pushes forward until SMA wire 112 isfully heated. This position may be somewhat ahead of a ratchet toothsuch that when cooled, bowel extender 10 relaxes back to the previoustooth. At the end of 10 seconds of heating, under loads in the range of0 to 50 gf (in steps of 10 gf), bowel extender 10 moved forward to aposition which is independent of the load, varying by at most 2.8%around an average value of 2.52 mm. This position may be just past aratchet step such that at the end of 20 seconds of cooling, bowelextender 10 can relax back to an average position of 2.47 mm (with avariance of 4.6% over load). In both the heated and cooled cases, thereis no significant trend over load: noise and randomness in frictionoutweighed the loading effects. After a second, and further repeatedheating/cooling cycles, bowel extender 10 displayed similar performance.The heated step motion was 10.5% larger than the predicted 2.28 mmheated step size. This difference can be attributed to theconservativeness of the prediction. Given that the 2.52 mm heated stepsize is equal to twice the 1.27 mm tooth spacing (within measurementerror), bowel extender 10 took two ratchet steps rather than one, whereeach thread is 1.27 mm. This double-stepping would not cause a problemin the application because it is repeatable and because the double stepsize generates an elastic bowel force well below the 20 gf safety limit.Thus, it is demonstrated that bowel extender 10 has both the force andmotion authority for the bowel application.

Under larger loads, ranging from 0 to 400 gf in steps of 50 gf, themotion was strongly dependent on the load and fell into threecategories: double steps, single steps, and no steps. From 0 to 150 gf,performance was similar to that in the application load range, and bowelextender 10 moved just past the second tooth and took a double step. Asthe load was increased from 0 to 150 gf, the actuated motion was largelyindependent of the load, decreasing by only 7.5% (from 2.53 mm to 2.34mm). This relative non-dependence on load is likely due to the fact thatthe ratchet tends to snap forward into place when approaching the nexttooth (a behavior not predicted by the conservative model) bringing themechanism farther forward than SMA wire 112 could do alone. From 200 to350 gf, bowel extender 10 moved past the first tooth, by an amountdependent on the load, and relaxed back to a single step. Since theactuated motion in this range does not bring the ratchet near to a tooth(except at the high load end), the load dependence of the motion is muchlarger, decreasing by 43% (from 1.94 mm to 1.36 mm) as the load wasincreased. This test result validates that bowel extender 10 canreliably take steps against loads much higher (by a factor of 17.5) thanthe designed load of 20 gf. From 400 to 500 gf, bowel extender 10 couldnot generate much motion at all and took no steps, moving at most 0.16mm when heated. While SMA wire 112 should have been able to generatemotion in this range, the load was too high for the ratchet mechanismwhich slipped, not allowing movable collar 108 to push push rod 100forward. Thus, the holding power of the ratchet was the forcelimitation, not SMA wire 112.

4.6. Ex-Vivo Experiments

To further validate the capabilities of the implant prototype and toprovide insights into the performance, additional tests were run withbowel extender 10 inside an actual bowel section. A section of bowelslightly longer than the 10 cm retracted length of bowel extender 10 wasremoved from a pig. The entire device was enclosed in a loose latex bagto protect it from fluids and to both electrically and thermallyinsulate SMA wire 112. Bowel extender 10 was placed inside the bowelsection and the ends of the bowel section tied closed to fit snuglyagainst the ends of bowel extender 10. The open end of the latex bagextended through the tied end of the bowel, the tie keeping both thebowel and the bag closed, through which the electrical connection wiresran. Bowel extender 10 was actuated using the KEPCO power supply,applying a step sequence of 0.8 A for 10 seconds with 15 seconds betweensteps.

The test indicated that the implant successfully elongated inside thebowel section, acutely stretching the bowel. These tests demonstratethat SMA bowel extender 10 fits into and operates in the actualintraluminal environment of the intestine. Were the bowel allowed togrow as bowel extender 10 extended over a longer period of time, theforces would have remained well within the capabilities of bowelextender 10, allowing bowel extender 10 to extend to its full 82%capacity.

4.7. Advantages and Technical Challenges of SMAs:

The foregoing indicates that the SMA device embodiment of bowel extender10 overcomes some of the shortcomings of the hydraulic expanderembodiment of bowel extender 10. As such, bowel extender 10 is of animplantable size, and it is anticipated that, the power supply andcontroller could similarly be implanted (in the manner of a pacemaker),with a telemetery unit designed to control the unit. Since the steps aresmall, discrete, and reliable, the motion that is generated is easilypredictable and controlled. A failsafe exists in bowel extender 10 inthat even if the actuation current is maintained for a long period oftime, bowel extender 10 will only take one step, and thus the boweltissue cannot be overextended without purposely cycling the current totake many steps in sequence. In addition, the stepping is consistent andthe ratchet mechanism rigidly holds its length after each step.

5. Additional Embodiments

Increased Expansion Of Bowel Extender 10: As discussed herein, SMA bowelextender 10 achieves an expansion of 82% over the initial length ofbowel. To produce a greater range of experimental data, in particular inconnection with a clinical device, a modified version of bowel extender10 (see FIG. 6 comprises two concentric linear ratchet mechanismsactuated by SMA wire 112, but moving in opposite directions. Thus, agreater than 2.5-fold expansion of the bowel will be achieved, allowingfor better assessment of the lengthening capacity of the bowel.

With particular reference to FIG. 6, bowel extender 10 comprises ahollow inner threaded rod 150 inside which a smaller threaded rod 100 isplaced. A second, reverse-oriented flap 152 is installed in outer shell102 which engages in threads 154 of hollow threaded rod 150. Areverse-oriented flap 156 on movable collar 108 engages the threads 154of the hollow threaded rod 150. Upon activation of the SMA, the movablecollar 108 will pull forward relative to outer shell 102, which willpush the hollow threaded rod 150 forward while the inner rod 100 is heldin place by the ratchet flap from outer shell 102. When the SMA relaxes,return spring 114 pushes movable collar 108 back, pushing the innerthreaded rod backwards with it while the hollow threaded rod is held inplace by the ratchet flap from outer shell 102. In this way, after onecycle, the outer threaded rod 150 moves forward a step, and the innerthreaded rod 100 moves backward a step, expanding bowel extender 10 fromboth ends. Supports for the inner threaded rod 100 will be mountedinside outer shell 102 to maintain rigidity as the inner rod 100 comesout of the hollow rod 150. Since bowel extender 10 expands out both endsfrom its initial length, it can expand to a theoretical maximum of threetimes its initial length. The actual expansion (2.5-fold) will be lessdue to the lengths required for the flaps and for overall rigidity.

Concept For Improving The Safety Monitoring And Control Of BowelExtender 10: To measure the tensile force bowel extender 10 is applyingto the bowel section, load cells may be placed on one or both ends ofbowel extender 10. While only one end is required to measure the appliedforce, the second end can be instrumented for redundancy, and to detectthe presence of uneven traction forces along the bowel section.Subminiature, very low profile force transducers are available, fromOMEGA (Stamford, Conn.) for example, with less than 10 mm diameter and 3mm thickness which can be mounted between the end of each threaded rodand its rounded siliconized bumper. Such devices have a 1.3 mm wire tocarry the force signal, which can be passed out along with the SMA powerwires. The extension length of bowel extender 10 may also be measured byradiopaque markers 29 (FIGS. 2A and 2B) at each end. The transduceroutput will be recorded via a National Instruments NI DAQ 6052-E dataacquisition card in a personal computer through Labview.

Monitoring The Expansion Of Bowel Extender 10: To monitor the expansionof bowel extender 10, and to ensure that bowel extender 10 actually doestake a step, a hall-effect sensor/permanent magnet pair can be mountedbetween two moving sections. In some embodiments, the hall effect sensorcan be mounted on the movable collar 108, and the permanent magnetmounted on outer shell 102. Small, low profile hall effect sensors withdimensions 4 mm×1.5 mm×3 mm are commonly available, for example fromALLEGRO MICROSYSTEMS INC. which can output a voltage in proportion tothe strength of a magnetic field. The distance to a small, rare-earthmagnet can be thus measured, and the incremental motion of theratcheting device detected. In this way, the motion at each step can bemonitored and both failed and double steps can be detected. By countingsuccessful steps, the overall extension motion can be recorded.

Lengthening Device With Implantation Into The Normal Enteric Flow,Without Creation Of A Separate Limb Of Bowel: Although creation of aseparate limb of bowel is acceptable, it could result in the loss ofintestine because of the surgical manipulation of the bowel andresection of the operated portions at both ends, thus not maximizing thelengthened segment of bowel created. Further, a second surgery on theintestine may be associated with severe adhesions and risks injury tothe intestine, itself. To address this, a more improved concept of atotally implanted device which is placed within the continuity of theintestine has been devised.

With particular reference to FIGS. 7 and 8, it can be seen that bowelextender 10 can be suspended within the lumen of the bowel. Fixationpoints 170 and 172 at both ends of bowel extender 10 will consist of abiocompatible material (such as polytetrafluoride (GORTEX)), but also amaterial of non-viable connective tissue (such as SURGISIS). Fixationpoints 170 and 172 can be a ring of material which is sewn to theintestinal lumen with either absorbable or non-absorbable suture. Thisfixation ring will be attached to the bowel extender at multiple pointsto equalize the creation of distractive forces circumferentially. Thediameter of bowel extender 10, in some embodiments, can be sized suchthat it is small enough that it will allow for enteric contents to movearound and/or between bowel extender 10 and the fixation rings 170, 172,thus, preventing an obstruction of the bowel.

With particular reference to FIGS. 10-15, bowel extender 10 can comprisean outer syringe casing 300 being generally elongated having a roundedend portion 302. Rounded end portion 302 can comprise a hydraulic well304 for receiving hydraulic fluid and a plurality of holes 306 forreceiving ties 308 (FIGS. 7 and 8) supporting fixation points 170, 172.Outer syringe casing 300 further comprises a plurality of stop members310 extending inwardly within an internal volume of outer syringe casing300. The plurality of stop members 310 are sized to engage acorresponding plurality of gaps formed in inner members to preventfurther extension thereof, as will be described.

Bowel extender 10 can further comprise an inner syringe casing 320 beinggenerally elongated having a rounded end portion 322. Rounded endportion 322 can comprise a hydraulic well 324 for receiving hydraulicfluid. Inner syringe casing 320 further comprises a plurality of stopmembers 330 extending inwardly within an internal volume of innersyringe casing 320. Inner syringe casing 320 still further comprises aplurality of gaps or depressions 332 formed in an exterior surface ofinner syringe casing 320. The plurality of gaps 332 are arranged andsized to engage with the plurality of stop members 310 to preventfurther extension thereof. The plurality of stop members 310 andplurality of gaps 332 can further comprise a complimentary slopedsurface 334 to permit simple collapse of bowel extender 10 when needed.

Inner syringe casing 320 can further comprise a seal member 336, such asO-rings, to aid in the fluidic sealing of inner syringe casing 320relative to outer syringe casing 300. Additional casings can be usedhaving similar construction as disclosed.

Control of the distracting forces (either hydraulic or electrical) aswell as the monitoring of tension and length of the expansion will becarried out through tube which will extend from bowel extender 10 itself(in the case of esophageal or small bowel lengthening) through thenares. In this setting, the patient would have a naso-enteric tubethroughout the duration of the lengthening procedure. In the case of alengthening of the large bowel, this catheter would either exit throughthe entire large and small bowel and out the nose, or exit via thestomach or through the bowel and abdominal wall.

In order to proceed beyond a 2.5-fold expansion, bowel expander 10 canbe curved in shape to fit within the abdominal cavity as it expandsbeyond the longest dimension of the cavity as illustrated in FIG. 9. Twopossible methods to achieve this include 1) constructing either thehydraulic, SMA ratcheting, or otherwise actuated expanders with acircular arc shape to each segment which form a longer arc length of thesame curvature when expanded, and/or 2) constructing either thehydraulic, SMA ratcheting, or otherwise actuated expander with flexibleelements which expanding linearly but can conform to the curvature ofthe abdominal cavity. As can be seen in FIG. 9, bowel extender 10 can bestraight (Line A), can curve a small portion (Line B) or can curve agreater portion (Line C), yet be maintained within the patient's bodycavity (Line D).

Upon achieving full extension and lengthening, bowel extender 10 can beretrieved with a flexible endoscope which can be introduced via themouth or anal canal, and the sutures fixing the fixation rings to thebowel wall can be cut, device retracted, and device removed either viathe mouth or anal canal.

6. Conclusion

Two devices developed as proof of concept for an implantable solution tobowel extension for the treatment of small bowel syndrome have beensuccessfully demonstrated. Using a simple hydraulic device, promisingresults in a study using pigs has validated the viability of the use ofmechanotransduction as a means to induce bowel growth. A shape memoryalloy based ratcheting device has demonstrated the possibility of afully implantable motion-controllable device.

Additional Embodiments and Discussion

A description of the occurrence, causes, and effects of Short BowelSyndrome (SBS) along with a description of the methods, high costs, andrelatively low effectiveness of existing treatments is discussed above.The discussion herein describes a relatively unexplored mode oftreatment using mechanotransduction where tensile forces on the bowelare employed to induce growth. A brief summary of the state of the artof mechanostransductive treatment devices follows:

The first class of existing devices referred to herein as externallymounted devices employs trans-body wall extension devices based on alinear screw which is mounted outside the body through a hole in theabdominal wall and into the and exposed segment of bowel which isremoved from continuity of the digestive tract. A screw is manuallyadvanced over time which applies tension to the bowel inducing growth.This class of device has been demonstrated successfully in rabbits andrats.

The second class of existing devices referred to herein assegment-implanted lengthening devices are implanted within a segment ofbowel which is removed from continuity of the digestive tract. Thedevice occupies (either inside or outside) the entire segment, and isactuated to lengthen over time, thereby applying distractive forces tothe bowel segment and inducing growth. Such a device may or may not beentirely contained within the lumen of the bowel, may or may not beentirely contained within the body, and may or may not be explicitlyattached to the bowel itself (where a device mounted inside the segmentwith the ends of the segment sutured closed simply pushes against theends from the inside as it lengthens). After lengthening, the device isremoved and the lengthened segment of bowel is re-inserted intocontinuity of the digestive tract.

The third class of existing device referred to herein as in-continuityimplanted lengthening devices are implanted within the bowel withoutrequiring the bowel segment to be removed from continuity. In this case,the device must not block the bowel, so fluids within the bowel must beable to flow around or through the device. The device is attached to thebowel at each end and the device is actuated to lengthen over time,thereby applying distractive forces to the bowel segment and inducinggrowth. Such a device may or may not be entirely contained within thebody, and may or may not reside inside the lumen of the bowel (it canattach from the inside or the outside). After lengthening, the device isdetached from the bowel at both ends and removed.

The second and third classes of existing devices have been discussedabove, namely a linear telescoping hydraulic device, and a linearratcheting device employing Shape Memory Alloy (SMA) actuation. Severalissues have been discussed in the background material of the presentapplication along with some concepts presented for enhancing theembodiments to address these issues. In particular, the following issueswere discussed:

Manifold expansion: since both classes of devices discussed above caninduce growth only up to the extent to which the device itself canexpand, to obtain large amounts of growth, the device itself must expandseveral times its original length (preferably 3 to 5 times). The aboveembodiments addresses this by adding a series of telescoping actuationstages to each embodiment which, while increasing the complexity of thedevice, can multiply the expansion capabilities.

Curvilinear expansion: to obtain large amounts of growth from an initialsegment, the classes of devices must themselves conform to the shape ofthe body cavity as the device lengthens. This was addressed above byeither shaping the devices in a circular arc, pre-shaped to conform tothe body cavity, or by constructing the devices to be flexible toconform to the body cavity. In both cases, the expansion capabilities ofthe device are enhanced but are still somewhat limited by the bodycavity shape.

Monitoring and Control: the above techniques cover general concepts andsome specific embodiments for adding sensing and monitoring capabilitieswith specific embodiments for including a load cell and for measuringincremental motion using a hall-effect sensor/magnet pair.

However, the following addresses new and different approaches fordevices for treating short bowel syndrome with novel methods in severalcategories of functionality: bowel attachment, expansion class, andmotion generation.

New Bowel Attachment Techniques

Two attachment approaches are discussed above: an end-abutting approach,where the bowel segment is closed off on the end and the device pushesagainst the closed end from the inside, and a sewn-in approach, where adisc, ring, web or other structure is sewn into the bowel from theinside. However, several additional approaches are covered in thisapplication including clamping (pinch), suction, and friction.

Clamping Attachment

The clamping approach shown in FIG. 16 employs a clamp from the outsideof the bowel (like a hose clamp) which compresses the bowel wall againsta portion of an internal device possibly against a groove. This has theadvantage over sewn-in approaches of very evenly distributing the loadalong the whole circumference of the bowel which may produce more even(and therefore possibly better or faster) growth whereas attachment withforce concentrations, at sutures, for example, may cause growth onlynear the stitch attachment points and may possibly damage the bowel atthose location. Clamping attachment also has the advantage overend-abutting approaches in that it can be accomplished without removingthe bowel segment from the continuity of the digestive tract, resultingin a less invasive surgery. This clamp approach could also be donemagnetically, or with elastic bands, etc.

Suction Attachment

The suction approach to attachment employs suction around a ring to holdthe bowel to an implanted device around its circumference. FIG. 17 showsa “suction puck” embodiment of this approach where suction is applied bya series of small holes around the circumference of a disk which isimplanted within the bowel. Suction can be produced, for example, bybuilding the puck with to rigid layers at the flat surfaces and abellows between actuated by, for example, SMA wires. When the SMA wirescontract, the bellows are compressed, expelling air from thecircumferential holes. When the SMA wires relax, the bellows expandunder their own elasticity, providing suction at the holes. Suction hasall the advantages of the clamp approach with the additional advantageof not requiring any components outside the lumen of the bowel,improving patient safety and comfort, and possibly not requiring anysurgery at all for insertion or removal. In addition, suction can beselectively engaged and disengaged after implantation, enabling othermodalities of bowel extension which will be described later.

Friction Attachment

Rather than explicitly attach to the bowel wall, friction can beemployed to produce a traction force from a device inside the bowel. Asimple embodiment would be a device which has a large enough diameter atthe ends to stretch the bowel circumferentially at those points, holdingthe bowel. Another embodiment would have radially expanding members atone or both ends to selectively engage and disengage the frictioncontact. Other embodiments could employ selective friction such as thefish scale concept shown in FIG. 18, where a directionally texturedmaterial provides high friction in one direction, producing tension,while enabling sliding in the other, enabling further modalities ofbowel growth described later. Friction attachments have similaradvantages to suction approaches with added simplicity ofimplementation, where directionally selective friction can be employedin a manner similar to selective suction.

New Classes of Bowel Expansion Methods

Previously, the only bowel growth modality used externally mounteddevices—in particular, external screws. The present discussion discussedboth segment-implanted lengthening devices and in-continuity implantedlengthening devices. New modalities are discussed in this document withdistinct advantages over the previous modalities including paying-outapproaches and track-following approaches.

Paying-out Approaches

Rather than requiring the device to extend to the full length of thegrown bowel segment as is by all the previously existing approaches,devices employing a paying-out approach maintain a relatively fixedlength (possibly with small reciprocating longitudinal motions) applyingtension to a fixed length of bowel, expelling the newly lengthened boweloff the end of the device as it grows. This motion can be incremental,where the device pulls on the bowel extending a small amount, allowsgrowth, releases the bowel, retracts, and reattaches to the bowel,analogous to a person paying out length from a coiled rope, one arm'slength at a time. Incremental paying out essentially acts as a ratchet,where the bowel itself plays a part of the ratchet mechanism itself.Alternatively, the motion can be continuous, analogous to extrusionprocesses in manufacturing. Paying out approaches have two very usefuladvantages: 1) one small device can grow bowel indefinitely, continuingto pay it out as it grows, and 2) no management of the path the bowelfollows is necessary since the grown bowel is allowed to move and settlefreely within the body cavity as it is paid out from the device.

Embodiments of incremental paying may employ any attachment method thatcan be selectively disengaged, pulled back, and reengaged including thesuction puck, fish-scale preferential friction (which natuarally engagesand disengages without control or actuation), etc, where the incrementalpull-back/push forward motion can be produced, for example, using an SMAwire—spring pair. One embodiment employing continuous paying out is theconveyor concept shown in FIG. 19, where one or more cyclic belts applytraction forces via friction to the bowel walls from the inside. Thesebelts pull the bowel relative to the fixed end of the device and expelit off the free end as the bowel grows. The friction could be enhancedby the use of an external clamping collar in a hybrid attachmentapproach employing both clamping and friction methods. While manypossibilities exist for actuating the conveyor belts in this embodiment,one possibility is to employ an SMA ratchet approach, shown in FIG. 20,where an SMA wire—spring pair produces a reciprocating motion which istransformed to a stepwise unidirectional motion of the belt through adirectionally selective ratchet mechanism.

Track-Following Approaches

While the previously existing expansion approaches require the device tolengthen as the bowel grows, the track-following approach uses a trackwhich is implanted in the bowel in continuity with a length and shapeequal to that of the desired final growth of a smaller portion of thebowel. The bowel is attached at one end of the track and atrack-following component starts along the track near the attached end.The bowel is attached to the track-following component defining theinitial length of bowel between the track following and fixed end of thetrack, which is preferably short relative to the entire length of track.The track following component is then caused to travel along the track,applying tension to the initial length of bowel. The initial length ofbowel grows, conforming to the shape of the track as the follower moves.The portion of the bowel initially over the track but not between thefixed end and the track-follower simply slides off the end of the trackas the follower moves. The track can be as long as the entire length ofexisting bowel allows, while the initial length can be arbitrarilyshort. Since the track defines the shape of the growing bowel as thetrack-follower moves, complex curvilinear paths can be obtained. Thetrack itself can be rigidly pre-shaped or even poseable to fit theparticular patient's body cavity as shown in FIG. 21.

Alternatively the track can be compliant to conform to the body cavitywhile still guiding the growth of the bowel. Track following has severalsignificant advantages over existing approaches: 1) it allows for muchlonger extension lengths within the geometric constraints of the bodycavity. 2) It does it in a way that is much simpler mechanically thanthe more obvious approach of building a curved hydraulic piston orcurved telescoping ratchet device, and 3) it allows customizable shapewith many degrees of freedom which can be adapted to the configurationof a particular patient's bowel.

One embodiment of track-following employs a crawler based on anSMA-driven ratchet to move along the track as shown in FIG. 21. Thebowel is attached at the front (as shown or alternatively the back) endof the main body of the device containing the power, sensing, andcontrol components and at the leading ring of the crawler assembly. Inthis embodiment, directional ratchet flaps (clutches) within the leadingand lagging rings of the crawler assembly (FIG. 22) allow each ring tomove only in the forward direction along the track. When the SMA wirecontracts, the lagging ring is pulled forward along the track by onestep. When the SMA wire relaxes, the return spring pushes the leadingtrack forward one step (FIG. 24). The assembly can negotiate the curvedtrack because the spring itself, concentric with the track, provides abendable connection between the two rings. Since the entire device isimplanted in the bowel, each component must have channels or holesthrough which fluids can flow (FIG. 26).

Another embodiment of track following uses the entire length of track asa rigid compression member, where a flexible element such as a cord orcable pulls the track-following element along the track. FIG. 26 showsan example of this embodiment where an SMA driven pulley at the free endof the track winds in a cable which pulls a suction puck (which could bereplaced by a movable component employing any attachment method) alongthe track. Note that while the figure shows a short straight track, along curved track is made possible by guiding the cable along curves ofthe track through a slot or series of rings attached to the track.Another modality for such a device in the case of a selectivelyengagable attachment such as the suction puck or fish-scale preferentialfriction is to pull the movable element along the track, disengage theattachment, pull the movable element back to the beginning of the trackusing, for example, a bias spring or second cable, reattaching, andrepeating the process. This forms a hybrid approach between paying outand track-following, enabling very large and rapid growth.

New Motion Generation Methods

Within any class of bowel extension, many methods exist for actuallyproducing the requisite motion. The embodiments discussed hereinemploying fluidic (hydraulic) and ratcheting (via SMA wires, forexample) methods can be used. However, additional methods for generatingmotion for bowel extension devices including passive motion anddistributed mechanism can be used.

Passive Motion Generation

Motion can be developed using a passive spring-like element rather thanan actively actuated element such as SMA or a hydraulic piston. Suchmethods start with a compliant structure compressed (or stretched in analternate mode of operation) to an initial length, implanted within thebowel attached at each end, and then allowed to expand over time,applying tension to the bowel as the bowel grows. Passive motion can beuncontrolled where the tensile force is determined by the current lengthof the device, and the extension rate is determined by the growthreaction of the bowel. Alternatively, the motion can be regulated wherethe spring is allowed to expand as determined by an actively controlledmechanism. The compliant member can be any axially compressiblestructure, so a coil spring, a webbing of foil, an accordion-likestructure, etc, and can be made of traditional materials (metal,plastic, etc) or alternatively, shape memory alloy working insuperelastic mode (for example).

FIG. 27 shows a coiled spring which is payed out over time to effectextension motion. While the paying out device is actuated in thisembodiment, the actual motion generated is entirely passive, and thusfundamentally different than our existing IP. This has the greatadvantage of being much simpler mechanically. Passive motion can beeither payed out in a controlled way, like the embodiment shown, or itcan be entirely uncontrolled where a compliant member is compressed(like a snake in a can) inside a bowel segment and the rate of expansionis entirely determined by the match between the force-deflectionproperties designed into the compliant member and the growth response tothese forces of the bowel. The compliant member can be any axiallycompressible structure, so a coil spring, a webbing of foil, anaccordion-like structure, etc, and can be made of traditional materials(metal, plastic, etc) or shape memory alloy working in superelastic mode(for example). Such methods have the great advantage of beingmechanically very simple and, depending on the control method, requirelittle or no power to produce motion. They also can work well in anin-continuity mode since it is straightforward to construct a compliantelement through which fluids may flow.

One embodiment of a passive expander is shown in FIG. 27, where a coilspring is allowed to expand as determined by a cable inside the spring.The cable is wound on a pulley which is allowed to rotate by, forexample, an SMA wire actuator. Note that the spring in this case can beinserted freely in the body, operating in a (segment or in-continuity)lengthening device mode, or can be installed over a curved track,operating in a track-following mode for enhanced expansion within theconfines of the body cavity. Note that the use of a track enables aneven simpler approach using, for example, an elastic band to pull thebowel along the track rather than a spring to push along it. The bandcan be looped over the end of the track and back again to provideexpansion along the full length of track. Many options exist foractuating the mechanism which allows the cable to unwind including afully-passive spring-escapement mechanism which is wound up like a watchbefore implantation allowing the main extension spring to expand in aregulated manner, requiring no power at all.

Another embodiment of a passive expander is shown in FIG. 28. Thisrotating-disk spring concept uses a spring which is compressed and heldaround a cylinder (also containing other components for power, sensing,and control). A rotating disk with an angled hole to allow passage ofthe spring wire is placed on one end of the cylinder. The spring threadsthrough this disk and connects to an end cap. When the disk rotates, thespring is let out through the hole in the disk, which will apply a loadto the end cap and, thus, the bowel. This disk is connected to a coilspring so that a moment is constantly applied to the disk. An SMA wireis connected to a plunger inside an escapement mechanism. Heating theSMA causes the wire to contract and when the wire cools the springforces it back to its original position. When these motions of the tabare accomplished, the rotating disk is allowed to spin in smallincrements, thus releasing the spring and applying a load on the bowelas shown in FIG. 29.

Distributed Mechanism

Motion for bowel extension can be generated through the use of adistributed mechanism which leverages motion from the actuatorthroughout the entire length of the device as it expands. Many differentjointed, compliant, and rotary linkages are possible to distribute themotion along the length, for example, a series of scissor mechanisms(like fireplace tongs or the comic boxing glove) with an SMA wireactuator at one end, where all portions ove the length of the deviceexpand. An alternative approach also employs distributed actuationthroughout the mechanism where each of a series of actuators inducesextension locally and their combined motion produces a bulk lengtheningof the device. These actuators can be all activated together a smallamount at a time, or each actuator can be fully activated one at a timeto incrementally expand the device. An embodiment of such an approach isshown in FIG. 30, where SMA wire segments mounted at each jointedsegment of a decoupled series scissor mechanism expand each segment oneat a time. Note that the distributed mechanism in this case can beinserted freely in the body, operating in a (segment or in-continuity)lengthening device mode, or can be installed over a curved track,operating in a track-following mode for enhanced expansion within theconfines of the body cavity. Also, passive expansion can be employed ateach joint, with discrete springs, for example, or even compliant jointswhich naturally expand. In this latter hybrid between passive expansionand distributed mechanism, the motion can be incrementally controlledwith (SMA actuated, for example) release latches which can allow eachsegment to expand out in series, thereby controlling the expansion.

1. A bowel extension device for implantation into a body comprising: a housing; a displaceable member movably coupled to said housing; and an actuation system moving said displaceable member from a retracted position to an extended position to apply a tensile force sufficient to promote bowel growth without causing damage to the bowel.
 2. The bowel extension device according to claim 1, wherein said housing and said displaceable member are configured to be completely disposed within said body after implantation of said bowel extension device.
 3. The bowel extension device according to claim 1, wherein said housing and said displaceable member are configured to be completely contained within the lumen of the bowel after implantation of said bowel extension device.
 4. The bowel extension device according to claim 1, wherein said displaceable member comprises a hydraulically actuated piston.
 5. The bowel extension device according to claim 1, further comprising an extension member composed at least partially of a Shape Memory Alloy, a first portion of said extension member coupled to said housing and a second portion of said extension member coupled to said displaceable member, said extension member configured to selectively move said displaceable member relative to said housing.
 6. The bowel extension device according to claim 1 wherein said displaceable member is positionable in a first position to define a first overall device length and a second position to define a second overall device length, said second overall device length being greater than twice said first overall device length.
 7. The bowel extension device according to claim 1 wherein said displaceable member is positionable in a first position and a second position to promote at least a two-fold increase in length of the bowel.
 8. The bowel extension device according to claim 1, further comprising: a first radiopaque sensor disposed at an end of said housing; and a second radiopaque sensor disposed at an end of said displaceable device opposite said end of said housing.
 9. The bowel extension device according to claim 1, further comprising: a first sensor disposed at an end of said housing; and a second sensor disposed at an end of said displaceable device opposite said end of said housing, said first sensor and said second sensor detecting a strain in the bowel.
 10. The bowel extension device according to claim 1, further comprising: a first sensor disposed at an end of said housing; and a second sensor disposed at an end of said displaceable device opposite said end of said housing, said first sensor and said second sensor detecting a force in the bowel.
 11. A bowel extension device for implantation into a body, said bowel extension device comprising: a first casing; a second casing telescopingly engaged with said first casing, said first casing and said second casing sized to receive a fluid therein urging said second casing apart from said first casing to exert a force upon a bowel to promote growth of the bowel.
 12. The bowel extension device according to claim 11 further comprising: a third casing telescopingly engaged with one of said first casing and said second casing, said third casing and said one of said first casing and said second casing being sized to receive a fluid therein urging said third casing apart from said one of said first casing and said second casing to exert a force upon a bowel to promote growth of the bowel.
 13. The bowel extension device according to claim 11, further comprising: a first radiopaque sensor disposed at an end of said first casing; and a second radiopaque sensor disposed at an end of said second casing opposite said end of said first casing.
 14. The bowel extension device according to claim 11, further comprising: a first sensor disposed at an end of said first casing; and a second sensor disposed at an end of said second casing opposite said end of said first casing, said first sensor and said second sensor detecting a force exerted in the bowel.
 15. A bowel extension device for implantation into a body, said bowel extension device comprising: a first casing; a second casing telescopingly engaged with said first casing; a drive system expanding said first casing and said second casing relative to each other, said drive system having a movable collar, a Shape Memory Alloy wire coupling said first casing and said movable collar, a ratchet system operably extending between said first casing and second casing preventing retraction of said first casing relative to said second casing, and a spring member opposing said Shape Memory Alloy wire such that upon excitation of said Shape Memory Alloy wire, said first casing is expanded relative to said second casing to exert a force upon a bowel to promote growth of the bowel.
 16. A bowel extension device for implantation into a body comprising: a housing; and a displaceable member coupled to said housing, said displaceable member being operable to apply a tensile force sufficient to promote bowel growth without causing damage to the bowel, said housing and said displaceable member configured to be completely disposed within said body after implantation of said bowel extension device. 